Y-90-labeled anti-cd22 antibody (epratuzumab tetraxetan) in refractory/relapsed adult cd22+ b-cell acute lymphoblastic leukemia

Abstract

The present invention relates to use of 90 Y-conjugated anti-CD22 antibody for treatment of relapsed/refractory acute lymphoblastic leukemia (ALL). Preferably the anti-CD22 antibody is epratuzumab tetraxetan. More preferably, the radiolabeled antibody is administered at a dosage of between 2.5 and 10.0 mCi/m 2 , most preferably on days 1 and 8 of the cycle. In specific embodiments, the dosage may be 2.5, 5.0, 7.5 or 10.0 mCi/m 2 . The radiolabeled antibody is capable of inducing a complete response in individuals with relapsed/refractory ALL.

What is claimed is: 
     
         1 . A method of treating refractory and/or relapsed B-cell acute lymphoblastic leukemia (ALL), comprising administering to a patient with refractory/relapsed B-cell ALL a  90 Y-labeled anti-CD22 antibody. 
     
     
         2 . The method of  claim 1 , wherein the  90 Y-labeled anti-CD22 antibody is epratuzumab tetraxetan. 
     
     
         3 . The method of  claim 1 , wherein the patient is refractory to treatment with at least one prior therapy. 
     
     
         4 . The method of  claim 1 , wherein the patient is refractory to treatment with an agent selected from the group consisting of vincristine, dexamethasone, prednisone, doxorubicin, daunorubicin, cyclophosphamide, L-asparaginase, etoposide, methotrexate, 6-mercaptopurine, a tyrosine kinase inhibitor and radiation therapy. 
     
     
         5 . The method of  claim 4 , wherein the tyrosine kinase inhibitor is selected from the group consisting of imatinib, dasatinib, nilotinib, bosutinib and ponatinib. 
     
     
         6 . The method of  claim 1 , wherein the patient is resistant/relapsed to multiple therapies. 
     
     
         7 . The method of  claim 1 , wherein the patient is positive for Philadelphia chromosome (BCR-ABL). 
     
     
         8 . The method of  claim 1 , wherein the humanized anti-CD22 antibody or fragment thereof comprises the light chain complementarity determining region (CDR) sequences CDR1 (KSSQSVLYSANHKYLA, SEQ ID NO:16), CDR2 (WASTRES, SEQ ID NO:17), and CDR3 (HQYLSSWTF, SEQ ID NO:18) and the heavy chain CDR sequences CDR1 (SYWLH, SEQ ID NO:19), CDR2 (YINPRNDYTEYNQNFKD, SEQ ID NO:20), and CDR3 (RDITTFY, SEQ ID NO:21). 
     
     
         9 . The method of  claim 1 , wherein the  90 Y-labeled anti-CD22 antibody is administered at a dose of about 100, 200, 300, or 400 MBq/m 2 . 
     
     
         10 . The method of  claim 1 , wherein the  90 Y-labeled anti-CD22 antibody is administered at a dose of between 90 and 400 MBq/m 2 . 
     
     
         11 . The method of  claim 1 , wherein the  90 Y-labeled anti-CD22 antibody is administered at a dose of between 2×370 MBq/m 2  one week apart per cycle. 
     
     
         12 . The method of  claim 1 , wherein the  90 Y-labeled anti-CD22 antibody is administered twice on days 1 and 8 of therapy, 
     
     
         13 . The method of  claim 1 , wherein the  90 Y-labeled anti-CD22 antibody does not induce a dose-limiting toxicity. 
     
     
         14 . The method of  claim 1 , wherein therapy with  90 Y-labeled anti-CD22 antibody is capable of inducing a complete response in the patient. 
     
     
         15 . The method of  claim 1 , wherein therapy results in a response lasting between 7 and 12 months. 
     
     
         16 . The method of  claim 1 , wherein an increase in serum Flt3-L concentration is predictive of therapeutic response, but not toxicity. 
     
     
         17 . The method of  claim 1 , wherein the  90 Y is attached to a DOTA moiety on the antibody or fragment thereof. 
     
     
         18 . The method of  claim 1 , further comprising administering a radiosensitizing agent to the patient. 
     
     
         19 . The method of  claim 1 , wherein the anti-CD22 antibody is RFB4.